کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5737432 1614722 2017 19 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Construct and face validity of a new model for the three-hit theory of depression using PACAP mutant mice on CD1 background
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Construct and face validity of a new model for the three-hit theory of depression using PACAP mutant mice on CD1 background
چکیده انگلیسی


- A three-hit theory-based new animal model for depression was tested.
- PACAP HZ mice with MD180 history upon CVMS showed depression-like phenotype.
- The lack or lower expression of PACAP interacts with BSTov-CRF, cpEW-Ucn1, DR-5-HT.
- Forced swim and marble burying tests supported the validity at behavioral level.
- BSTov-CRF, cpEW-Ucn1, DR-5-HT neurons were affected in PACAP HZ mice.

Major depression is a common cause of chronic disability. Despite decades of efforts, no equivocally accepted animal model is available for studying depression. We tested the validity of a new model based on the three-hit concept of vulnerability and resilience. Genetic predisposition (hit 1, mutation of pituitary adenylate cyclase-activating polypeptide, PACAP gene), early-life adversity (hit 2, 180-min maternal deprivation, MD180) and chronic variable mild stress (hit 3, CVMS) were combined. Physical, endocrinological, behavioral and functional morphological tools were used to validate the model. Body- and adrenal weight changes as well as corticosterone titers proved that CVMS was effective. Forced swim test indicated increased depression in CVMS PACAP heterozygous (Hz) mice with MD180 history, accompanied by elevated anxiety level in marble burying test. Corticotropin-releasing factor neurons in the oval division of the bed nucleus of the stria terminalis showed increased FosB expression, which was refractive to CVMS exposure in wild-type and Hz mice. Urocortin1 neurons became over-active in CMVS-exposed PACAP knock out (KO) mice with MD180 history, suggesting the contribution of centrally projecting Edinger-Westphal nucleus to the reduced depression and anxiety level of stressed KO mice. Serotoninergic neurons of the dorsal raphe nucleus lost their adaptation ability to CVMS in MD180 mice. In conclusion, the construct and face validity criteria suggest that MD180 PACAP HZ mice on CD1 background upon CVMS may be used as a reliable model for the three-hit theory.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 354, 23 June 2017, Pages 11-29
نویسندگان
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